Evaluation of the Heparin Binding Protein Levels in Sepsis

Sepsis is a heterogeneous disorder caused by an invasive infection that results in host inflammatory response. The underlying pathogenesis is complex and dependent on the etiologic microorganism, site of infection, and host factors. Present criteria defining sepsis (including change of body temperature, increased heart and respiration rates, and leukocytosis/leukopenia) are non-specific making it difficult to distinguish sepsis from other diseases and in particular to predict which patients are likely to become more severely ill. The consensus definition of sepsis has been debated over the past years and one suggested approach is to focus more on the presence of organ dysfunction. In standard care, patients at risk of becoming more seriously ill are not identified nor indicated for resuscitative efforts until they develop hemodynamic insufficiency or organ failure. However, after progression to severe disease mortality increases significantly. A recent study showed that almost a quarter of patients presenting with uncomplicated sepsis in an Emergency Department (ED) developed severe sepsis or septic shock within 72 hours. Delayed in-hospital progression to increased organ dysfunction was associated with increased transfer to the intensive care unit (ICU) and increased hospital length of stay. The identification of risk patients can lead to earlier initiation of resuscitation therapies and potentially lead to reduced morbidity and mortality. There are also increasing evidence that a single episode of severe sepsis has negative impact on quality of life and mortality several years after the actual incident. Also, recent studies indicate that less severe organ dysfunction, such as small increases in serum creatinine, are associated with increased long-term mortality among sepsis survivors.

Mechanisms that trigger the release of heparin-binding protein (HBP) from neutrophils in the presence of bacteria have previously been reported. HBP has several functions such as a chemo-attractant and as an activator of monocytes and macrophages. Also, it induces vascular leakage by interacting with the capillary endothelium and breaking cell barriers. In vivo studies have demonstrated that HBP released by the complex formed by the group A streptococcal M1 protein and fibrinogen induces a massive tissue edema contributing to severe organ damage. In clinical investigations, the release of HBP has been demonstrated in various infectious diseases caused by a wide array of bacteria. A recent single-center study of patients admitted for suspected infection and fever showed that plasma levels of HBP were significantly higher among patients who presented with or developed severe sepsis with circulatory failure.

A prospective observational study in a tertiary care Emergency Department. Patients must be identified and enrolled within 72 hours of qualifying inclusion criteria. At this time, unused blood samples collected for routine testing will be examined and the plasma level of HBP will be recorded; only blood samples processed by the lab within 3 hours of collection will be used. In addition, physiologic variables detailed in the data elements section, including mental status, metabolic, renal, heme, hepatic, respiratory, cardiovascular, resuscitation, and vasopressor use will be recorded. Patients who meet the inclusion criteria will be identified. Researchers will collect and record a resuscitation summary for a span of 4 hours; this data, outlined in the data elements section, will be linked to the quality improvement (QI) database of Sepsis Research. Additionally, the patient's HBP plasma levels will be measured from unused blood samples collected for routine lab testing time (T) 24, 48, and 72-hours (T24, T48, T72) after meeting the inclusion criteria (T0); resuscitation summaries will also be collected at T24, T48, T72. For patients meeting sepsis alert criteria, T0 will be defined as the time that the patient qualified; those enrolled based on Predisposition, Injury, Response, Organ dysfunction (PIRO) score will have T0 defined as the time hospital admission was ordered. Patients will be followed throughout their time in the hospital and their outcomes will be recorded.

Inclusion criteria

• Clinical diagnosis of a bacterial or viral infection
• 18 years or older
• Meet the sepsis alert criterion (Hypotension (BP < 90 after 2 L of fluids or lactate ≥ 4) OR
• PIRO (Predispose, Infection, Response, Organ dysfunction ) score ≥ 15 .

Exclusion criteria

• Minors (less than 18 years of age)
• Patients who do not meet sepsis criteria as described above